Glatiramer acetate in situ forming gel, a new approach for multiple sclerosis treatment.

Autor: Shobeirean A; Department of Chemical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran., Attar H; Department of Chemical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran., Varshochian R; Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. varshochian@sbmu.ac.ir., Rezvanfar MA; Department of Toxicology and Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Jazyk: angličtina
Zdroj: Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences [Daru] 2024 Dec; Vol. 32 (2), pp. 649-664. Date of Electronic Publication: 2024 Sep 03.
DOI: 10.1007/s40199-024-00532-z
Abstrakt: Background: Glatiramer acetate (GA), a commonly used treatment for multiple sclerosis (MS), requires long-term frequent injections to ensure its effectiveness. This often leads to adverse effects, patient noncompliance, and economic inefficiency.
Objectives: In this study, poloxamer, as a thermosensitive polymer modified by chitosan (CS) and hyaluronic acid (HA), was employed to prepare an in situ forming prolonged release formulation of GA to overcome the problems derived from frequent repeated injections and to enhance the patient compliance.
Methods: The sol-gel formulation was produced through a cold method and optimized using design of experiments. The final product was characterized in terms of gelation time (GT), rheological behaviors, morphological properties, assay, and drug release kinetics.
Results: The in vitro release rate of GA during the first 24 h was quite rapid, but then it continued at a slower rate of 0.05 mg ml -1 h -1 . The in vivo analysis after the subcutaneous injections showed lower levels of IL-5, IL-13, and uric acid (UA) in mice treated with the gel formulation compared with those receiving free GA in the first few days. However, after 10 days, significantly higher concentrations were detected, which continued to increase slowly.
Conclusion: It can be concluded that the designed thermosensitive sol-gel formula is capable of extending the effectiveness of GA and can be considered as a promising sustained release formulation for the treatment of MS.
Competing Interests: Declarations Statement of human and animal rights The animal studies were performed after receiving approval of the animal ethics committee of the Institutional Animal Care of Islamic Azad University-Science and Research Branch under the Ethic code of IR.IAU.SRB.REC.1401.224,Tehran, Iran. The experiments were performed in adaccordance with the guidelines for the Care and Use of Laboratory Animals of the National Institute of Health. Conflict of interest All authors declare that they have no conflict of interest.
(© 2024. The Author(s), under exclusive licence to Tehran University of Medical Sciences.)
Databáze: MEDLINE